Now, disease genes that target disease-specific genomic structure abnormalities have been identified, and accordingly, a multiplicity of genes associated with diseases, such as cancer, have been found. These are attracting attention as a diagnostic biomarker for diseases. As the expression of a biomarker cannot always satisfactorily be realized at an early date of disease development, the diagnosis by the detection of a biomarker is not always appropriate as an early diagnosis.
The early diagnosis is absolutely necessary from the viewpoint of improvement in cure rate and relieving the burden on patients. As an approach therefor, it is contemplated to observe an early change of disease development by detecting an abnormality of genomic modification and, accompanying the same, a change of promoter activity.
The change of promoter activity regulates the probability of gene expression, and is observed earlier than the expression of disease-associated gene and disease-associated protein.
A reporter gene assay is available as a method of detecting the condition of activation of a particular promoter within a cell. The reporter gene assay is a method comprising linking a reporter gene for visualizing the promoter activity, such as GFP, β-galactosidase or luciferase gene, downstream of a promoter of interest to thereby obtain a reporter construct, introducing the reporter construct in a test cell, and quantifying the condition of promoter activation on the basis of the activity of expressed reporter protein. The reporter gene assay, as a method of quantifying a cellular promoter activity, is mainly used in in-vitro diagnosis. Performing in vivo the reporter gene assay in a non-invasive manner is being tested in animal experiments. However, such tests all use optical detection methods. Therefore, they pose, for example, the problem that the luminescence and/or fluorescence in a deep area (approximately 2 cm or more) of the body is attenuated, so that the scope of application of the reporter gene assay is limited to a shallow part of the body and the like.